Dataset Information

Multimodal characterization of the effects of stimulation on the human brain ex vivo and in vivo.

ABSTRACT: The underlying mechanisms of therapeutics using brain stimulation in humans are not understood. In particular, it is unknown how brain stimulation impacts gene expression in acute and chronic temporal periods. Although therapeutic approaches like deep brain stimulation are becoming more widely used, it is impossible to study stimulation-induced genetic changes without tissue samples which at best could be collected post-mortem. To overcome these extremely limiting circumstances, we have implemented a multi-part experimental design involving single cell resolution RNA and ATAC sequencing of human cortex that has been stimulated in several paradigms. In the first, acute human cortex slices are stimulated with a high-density microelectrode array, which allows us to track how neural activity changes after stimulation together with genomic changes. In the second, tissue is collected from neurosurgery patients immediately after direct cortical stimulation in vivo. We have uncovered differentially expressed genes and differentially accessible chromatin regions in both paradigms. We have also determined the impact of stimulation on cell assembly plasticity and celltype-specific changes in firing patterns. Our integrated approach of applying stimulation paradigms in human brain tissue both in vivo and ex vivo has not been completed before. These results represent a key first step in our quest to understand exactly how brain stimulation supports neural function at the cellular level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288939 | GEO | 2026/06/06

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Sub-thalamic deep brain stimulation (DBS) reversibly modulates ParkinsonM-bM-^@M-^Ys disease (PD) motor symptoms, providing an unusual opportunity to compare leukocyte transcripts in the same subjects before and after neurosurgery and after disconnecting the stimulus (ON-and OFF-stimulus). Here, we report rapid stimulus-induced and largely reversible changes in PD leukocyte transcripts, which were larger in scope than the disease-induced changes. These transcript changes classified advanced pre- from post-surgery PD patients and discriminated patients from controls. Moreover, the extent of changes correlated with the neurological efficacy of the DBS neurosurgery, and covered both regulatory pathways and individual transcript changes, e.g. SNCA, PARK7 and the splicing factor SFRS1. Following 1 hour OFF-stimulus, these changes were largely reversed. We extracted from these differences a modified transcripts signature which discriminated controls from advanced PD patients, pre- from post-surgery and ON-from OFF-stimulus conditions. A further gene-list independent analysis detected reversed pathways. Our findings suggest future uses of this approach and the discovered molecular signature for early diagnostics of PD and for identifying novel targets for therapeutic intervention in this and other DBS-treatable neurological diseases. 27 Total samples were analyzed. Study design included four conditions. PD patients (n=7) leukocyte blood samples were examined at 3 time points, and healthy control subjects (n=6) were examined once each. Samples were taken 1 day prior to sub-thalamic nucleous (STN) DBS treatment, several months after STN-DBS treatment upon optimal stimulation and following one hour electrical stimulation cessation. The off stimulation caused recruitment of the disease symptoms as measured by the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III). The different stages are designated: S1 (pre-treatment), S2 (post STN-DBS) and S3 (upon off stimulation). All patients were on dopamine replacement therapy (DRT) when examined pre- and post-DBS off stimulation (albeit with reduced therapy dose post-DBS). To reduce biological variability among the samples which is not related to the study, only male subjects were included in this study. Samples from six age- and gender- matched healthy control subjects served to detect disease modified transcripts and for pre- and post- treatment comparisons. The study was approved by the human review board at the Hadassah University Hospital, Ein-Kerem (no. 6-07.09.07) in accordance with the Declaration of Helsinki. All study participants signed informed consent.

Dataset Information

Multimodal characterization of the effects of stimulation on the human brain ex vivo and in vivo.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets